FEATURE ARTICLE
Why We Develop Food Allergies
Coached by breast milk and good bacteria, the immune system strives to learn the difference between food and pathogens before the first morsel crosses our lips
Per Brandtzaeg
Alarm Calibration
Microorganisms existed billions of years before the first immune systems. Rather than waging war on them, our immune systems evolved a mutually beneficial partnership (mutualism) with certain bacterial strains that would compete for resources, in the environment of the gut or on other body surfaces, with more harmful microbes. An average adult carries 1014—100 million million—bacteria in his gut, or about 10 times more bacterial cells than there are human cells in the body. Our mechanisms of defense are shaped by this mutualism.
According to the original hygiene hypothesis, reduced or aberrant microbial exposure early in infancy doesn't provide enough stimulation to the so-called helper T cell type 1 (Th1). As a result, Th1 cells don't sufficiently antagonize the other type of helper T cell, Th2. Without this suppression, Th2 cells release cytokines that induce B cells to produce too much IgE, leading to atopy. Thus, the right commensal microbiota promotes mucosal homeostasis by helping to shift the newborn's immune system from a state dominated by Th2 signals (the allergy track) to one in which the cytokine profile is more balanced.
The extended hygiene hypothesis postulates that Treg cells, which have identifying proteins called CD25 receptors on their surfaces, are an important part of the homeostatic mechanism. Treg cells limit Th1 and Th2 cells when they act as proinflammatory effector T cells, thereby avoiding inflammation and tissue damage. Treg cells also suppress immune responses indirectly, either by reducing APC function or by secreting suppressive cytokines.
The window for fine-tuning a baby's mucosal immune system is relatively narrow, starting when the infant is colonized with vaginal and intestinal bacteria from the mother's birth canal. In healthy individuals, this initial exposure shifts the Th2-skewed cytokine profile of the newborn toward a Th1 profile, a sign of immunological maturation. But in atopic children, cytokines from Th2 cells continue to predominate, increasing the output of IgE, which predisposes the newborn to later allergy. Fortunately, the system retains some plasticity. Infants may be able to correct their ratio of Th2 to Th1 responses, and most children with overt food allergy outgrow it. (Some reactions, such as peanut sensitivity, are more likely to persist.) As alluded to above, there is hope for the future in that Treg cells can be stimulated intentionally through bacterial or parasitic products.
Clearly some stimuli are better than others at balancing the immune system. Several studies have reported that atopic infants have more of the intestinal bacterium Clostridium and less bifidobacteria in their stools than non-atopic controls. Similarly, another study found that children in Sweden tended to have more clostridia as well as allergies, whereas an age-matched group in Estonia had fewer allergies and high levels of lactobacilli and eubacteria. This research raises the possibility that various feeding and treatment regimens (particularly antibiotics) could exert long-term effects on the developing immune system through the composition of the gut microbiota. Certainly the possibility of promoting immune homeostasis through probiotic adjustment of the gut microbiota deserves further research.
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